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Haematology > Leukocytosis (includes leukaemia) > Flashcards

Leukocytosis (includes leukaemia) Flashcards

1
Q

Typical ages of leukaemia presentations?

A
  • ALL: children and older adults
  • CML: 40 - 60y
  • AML, CLL: >60y
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2
Q

Leukemia v lymphoma?

A

-Leukemia: malignant cells arise in bone marrow and may spread elsewhere (inc blood and bone marrow).
-Lymphoma: malignant cells arise in lymph nodes/tissues and may spread elsewhere (inc blood and bone marrow).
Location where malignant cells are found does not solely define malignancy: classified on cell characteristics.

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3
Q

What is AML?

A

Rapidly progressive malignancy characterised by failure of myeloid cells to differentiate beyond blast stage.

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4
Q

Epidemiology AML?

A
  • Incidence inc w/ age (median onset = 65y)

- 10-15% childhood leukemias

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5
Q

RFx AML?

A
  • myelodysplastic syndromes
  • benzene
  • radiation
  • alkylating agents as treatment for previous malignancy
  • Infections e.g. adult T cell leukaemia lymphoma and HTLV1
  • Genetics e.g. trisomy 21, high risk AML
  • Rare familial syndromes (e.g. Fanconi’s anemia)
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6
Q

What does uncontrolled progression of blasts in marrow lead to?

A
  • suppression of normal haematopoietic stem cells
  • appearance of blasts in peripheral blood
  • accumulation of blasts in other sites (skin, gums)
  • metabolic consequences; tumour lysis syndrome
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7
Q

Blood alterations in AML?

A
  • Anemia
  • Thrombocytopenia
  • Neutropenia (even w/ normal WBC)
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8
Q

What causes skeletal pain and bony tenderness in AML?

A

Accumulation of blast cells in marrow

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9
Q

What is leukostasis / hyperleukosis syndrome?

A

Medical emergency.
Large numbers of blasts interfere with circulation and lead to hypoxia and haemorrhage - can cause diffuse pulmonary infiltrates, CNS bleeding, resp distress, altered mental state, priapism.

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10
Q

What are the metabolic effects of AML?

A
  • Increased uric acid -> nephropathy, gout
  • Release of phosphate -> decreased Ca2+, decreased Mg2+
  • Release of procoagulants -> DIC
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11
Q

Why is PO4(3-) increased in AML?

A

PO4(3-) is released by leukaemia blasts.

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12
Q

Bloods in AML?

A
  • FBE: anemia, thrombocytopenia, variable WBC
  • INR / aPTT
  • Fibrin degradation products / fibrinogen (in DIC)
  • Increased LDH
  • Increased uric acid
  • CMP: Increased PO4 (3-), Decreased Ca2+
  • Peripheral blood film
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13
Q

Findings on peripheral blood film in AML?

A
  • Circulating blasts with Auer rods (azurophilic granules) ==> pathognomonic for AML.
  • Changes to multiple lineages typical esp cytopenias resulting from suppression of normal haematopoiesis.
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14
Q

Bone marrow aspirate findings in AML?

A

-Blast count >20% (N =

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15
Q

Other Ix in AML work up? (non blood, non BMA)

A
  • CXR: r/o pneumonia
  • ECG
  • MUGA scan (pre chemo; cardiotoxic)
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16
Q

AML treatment strategy?

A
  1. Induction: induce complete remission of AML
    Check BMA response
  2. Consolidation: prevent recurrence e.g. intensive consolidation chemotherapy, stem cell transplantation
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17
Q

Supportive care in AML treatment?

A
  • Screen for infection: Regular MCS of all sites possible
  • Fever: MCS all sites, CXR, ABx
  • Platelet and RBC transfusions
  • prevent metabolic abnormalities (eg. allopurinol)
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18
Q

Acute v chronic wrt leukemia?

A

Characterises the clinical presentation and response to therapy of the condition.

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19
Q

Clinical presentation of acute leukaemia?

A

-Anemia: lethargy, dyspnoea, pallor, presyncope
-Neutropenia: FCR, infections
-Thrombcytopenia: bruising, bleeding
-B symptoms: fevers, sweats, weight loss
-Organ infiltration
Rarer: lymphadenopathy, hepatosplenomegaly, symptoms of hyperleukocytosis

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20
Q

What is immunophenotyping?

A

Intensity with which a fluorescence-conjugated Ab stains cell surface proteins: if strong staining, cell surface protein present.

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21
Q

What is the first lab test in leukaemia work up?

A

Immunophenotyping using flow cytometry:
-determines pattern of acute leukaemia through surface antigen expression i.e. AML v ALL stain for myeloid vs lymphoid markers

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22
Q

What is another use for flow cytometry immunophenotyping beyond determining pattern of leukaemia?

A
  • Identifying aberrant expression (80% acute leukemias).

e. g AML blasts may express a lymphoid antigen.

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23
Q

What are the cytogenetic risk groups in AML?

A

Used to inform prognosis.

  • GOOD: t(8;21), inv 16, t(15;17)
  • INTMED: mostly normal cytogenetics
  • POOR: monosomy 7, multiple complex abnormalities, chr 3 abnormalities.
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24
Q

What is the role of molecular testing in AML?

A
  • Defining mutations with prognostic significance
  • Diagnosing specific translocations to confirm cytogenetic findings
  • Quantifying transcript to monitor treatment response
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25
Q

How is prognosis determined in AML?

A

AT Dx: cytogenetics, molecular findings
DURING Rx:
-flow cytometric evidence of residual disease
-disappearance of previous cytogenetic abnormalities

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26
Q

How is response to therapy monitored in acute leukaemia?

A
  1. BMA and trephine:
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27
Q

Main chemotherapy induction drugs?

A

Cytarabine
+
an anthracycline e.g. idarubicin (cardiotoxic)

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28
Q

Specific additions to standard therapy in ALL treatment?

A
  • Maintenance therapy post consolidation: 2-3y to prevent relapse
  • Multi drug Rx e.g. L-asparaginase
  • Intrathecal chemo due to RR CNS relapse
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29
Q

What is APML?

A

Acute promyelocytic leukemia: ass/w t(15:17) ==> forms PML/RARa.
New therapies: now one of most curable leukemias!!

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30
Q

What is the major feature of APML presentation?

A

Bruising and bleeding

31
Q

Coagulation study results in APML?

A

DIC with low fibrinogen (due to release of pro-coagulants from malignant promyelocytes)

32
Q

APML morphological characteristics?

A

Faggot cells containing many Auer rods.

33
Q

Cytogenetics of APML?

A

t(15;17): translocation of retinoic acid receptor (RARa) on 17 w/ promyelocytic leukemia gene (PML) on 15 ==> PML-RARa.

34
Q

Mx APML?

A
  • Correct coagulopathy: platelets, cryoprecipitate and fibrinogen as needed
  • All trans retinoid acid (ATRA) induces promyelocyte differentiation.
  • arsenic
35
Q

Epidemiology ALL?

A

-75%

36
Q

What is ALL?

A

Malignant disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal haematopoietic cells of the bone marrow.

37
Q

How is ALL subdivided?

A

Cell of origin (B or T)

38
Q

Symptoms of organ infiltration in leukemias?

A
  • Gingivial hypertrophy (may present to dentist!)
  • Hepatosplenomegaly (ALL)
  • Lymphadenopathy
  • Skin: leukemia cutis
  • Gonads (ALL)
  • Eyes: Roth spots, cotton wool spots, vision changes
39
Q

How can leukemia symptoms be rationalised / categorised?

A

Categorised as due to:

  1. Bone marrow failure: anaemia, thrombocytopenia, neutropenia
  2. Organ infiltration: tender bones, lymphadenopathy, hepatosplenomegaly, meningeal signs.
40
Q

ALL good prognostic factors?

A
  • Young

- WBC

41
Q

Prognosis ALL?

A

-Kids 80% long term remission

Adults only 30-40% 5y survival

42
Q

Cytogenetic indicators of ALL prognosis?

A

POOR: t(4;11)
GOOD: t(9;22) now good with tyrosine kinase inhibitor therapy

43
Q

How is need for allogeneic marrow transplant determined?

A

-Age (

44
Q

What is CML?

A

Myeloproliferative disorders characterised by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate.

45
Q

Epidemiology CML?

A

Any age group. Median age 65y

46
Q

Pathophysiology CML?

A

Ph Chr = t(9;22) forming bcr-abl fusion gene, an active tyrosine kinase.

47
Q

What are the 3 phases of CML?

A
  1. Chronic Phase (85% pts)
  2. Accelerated Phase
  3. Blast Crisis
48
Q

What is the chronic phase of CML?

A

-Few blasts (

49
Q

What is the accelerated phase of CML?

A

Impaired neutrophil differentiation

  • circulating blasts (10-19%) w/ increased peripheral basophils (pruritus)
  • FBE: thrombocytopenia
  • worsening constitutional symptoms
  • splenomegaly (extramedullary haematopoiesis)
50
Q

What is the blast crisis phase of CML?

A

Aggressive course: blasts fail to differentiate.

  • blasts (>20%) in peripheral blood or marrow
  • reflects acute leukemia
51
Q

Clinical presentation CML?

A

Many pts asymptomatic / non-specific Sx

-2” Splenic involvement:early satiety, shoulder tip pain, splenomegaly

52
Q

Peripheral blood film features CML?

A

-Leukoerythroblastic picture: immature RBCs and granulocytes present e.g. myelocytes and normoblasts

53
Q

BMA features in CML?

A
  • Myeloid hyperplasia with left shift
  • increased megakaryocytes
  • mild fibrosis
54
Q

Symptomatic treatment CML?

A

Allopurinol and antihistamines

55
Q

Chronic phase treatment CML?

A

Imatinib (Gleevec): tyrosine kinase inhibitor in bcr-abl cells ==> inhibits proliferation and induces apoptosis.
If loss of response, trial 2nd/3rd generation inhibitors.

56
Q

Treatment accelerated / blast phase CML?

A
  • Refer for clinical trial 2nd/3rd gen TKIs

- Prepare for allogeneic stem cell transplant

57
Q

How is treatment success determined in CML?

A

Therapeutic miletones:

  • Haem: improved WBC and plt counts, reduced basophils
  • Cytogenetic: undetectable Ph-Chr in bone marrow
  • Molecular: reduced / absent bcr-abl in periphery and marrow
58
Q

Prognosis acute phase CML?

A
  • 2/3 develop AML picture (unresponsive to remission induction)
  • 1/3 develop ALL picture
59
Q

Ix in CML?

A
  • FBE: leukocytosis w/ early myeloid cells, basophils, eosinophilia
  • BMA: hypercellular
  • Cytogenetics: t(9;22)
  • Molecular: bcr-abl
60
Q

CML response monitoring post therapy?

A

PCR monitoring of bcr-abl transcript in peripheral blood every 3/12 aiming for major molecular response (MMR) =

61
Q

What are the second generation TKIs used when imatinib no longer effective?

A

Dasatinib

Nilotinib

62
Q

What is CLL?

A

Indolent disease characterised by clonal malignancy of mature B cells.

63
Q

Epidemiology of CLL?

A
  • most common leukemia
  • mainly older puts; median 65y
  • M>F
64
Q

Pathophysiology of CLL?

A

Accumulation of neoplastic lymphocytes in blood, bone marrow, LNs and spleen

65
Q

What are the features of immune dysregulation due to CLL?

A
  • ITP
  • AI haemolytic anemia
  • Hypogammaglobulinemia
  • +/- neutropenia
66
Q

What are smudge cells?

A

Artifacts of damaged lymphocytes from slide preparation

67
Q

Ix in ?CLL?

A
  • FBE: aboslute lymphocytes >5x10^9 w/ a CLL phenotype
  • Film: lymphocytes small and mature, smudge/smear cells
  • Flow cytometry
  • Cytogenetics: FISH
  • BMA: lymphocytes >30%
  • CT: staging
68
Q

Natural history CLL?

A

Indolent but incurable; slow progression.

69
Q

Treatment CLL?

A

Based on symptoms symptoms:
-observation if asymptomatic
-fludarabine + cyclophosphamide + rituximab
-corticosteroids, IVIG for ai phenomena
Allograft only curative; majority ineligible.

70
Q

How is CLL prognosis determined?

A

Rai staging. Risk =

  1. LOW: lymphocytes blood and marrow only
  2. MID: lymphocytosis with enlarged nodes in any site / hepatosplenomegaly
  3. HIGH: lymphocytosis with disease related anaemia or thrombocytopenia
71
Q

Complications of CLL?

A
  • Bone marrow failure
  • immune complications (AIHA, ITP, immune deficiency)
  • gammopathy
  • hyperuricemia w/ Rx
  • 5% undergo Richter’s transformation
72
Q

What is Richter’s transformation?

A

Aggressive transformation of CLL to diffuse large B-cell lymphoma.

73
Q

Immunophenotype CLL?

A

-Immunophenotype: B lymphocytes co expressing CD5 (not normal) and CD-19/-23.

74
Q

Cytogenetics in CLL? How can inform prognosis?

A

FISH.

  • Indolent course: del 13q
  • Aggressive course: del 17p (w/ loss of p53)

Haematology (25 decks)

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